This is a competing renewal of a cooperative research agreement for a Sexually Transmitted Diseases Research Center (STD CRC). A total of five project and 3 cores are included, including studies on the STD pathogens N. gonorrhoeae, H. ducreyi, and T. pallidum and an epidemiological/behavioral study on adolescent sexual behaviors and outcomes. Work on the scientific projects will be facilitated by an administrative core, a clinical microbiology core, and human challenge core. These studies will unit the scientific areas of basic microbiology and immunology, clinical infectious diseases, and behavioral and epidemiological research. Within these scientific areas there are multiple interactions of the scientific disciplines of molecular microbial genetics, immunology, epidemiology, behavioral research, and biostatistics and mathematical modeling. This work will be conducted at the University of North Carolina-Chapel Hill and its affiliated sexually transmitted disease. The proposed work is, for the most part, a direct follow-up on successfully completed projects of th4e past STD CRC. The first project will study the pathogenesis and immunology of gonococcal outer membrane proteins involved in iron utilization from hemoglobin and heme. The second project will study the importance of gonococcal opacity proteins and pili for infection in the human volunteers. The third project will focus on studies of attachment of H. ducreyi to human neutrophils and epithelial cells. The fourth project will explore potential phase and antigenic variation of newly discovered outer membrane proteins of T. pallidum. The five project is a behavioral and epidemiological study of adolescents who have been followed by the ADHEALTH project, which aims to understand the particular health seeking behaviors related to testing for STDs and treatment of STDs. Overall these projects will help to understand the immunobiology and several important bacterial STDs and may help to develop vaccines to prevent these diseases. These projects also will help to understand interventions at the clinical level which might help reduce STDs particularly in adolescents.